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PURPOSE: To assess the safety and efficacy of ripasudil for retinopathy of prematurity (ROP). STUDY DESIGN: Phase 1/2, multicenter, open-label, single-arm, 12-week clinical trial. METHODS: Infants born with gestational age (GA) of ≤ 32 weeks or weight of ≤ 1500 g with zone I or II, ≥ stage 1, ROP in both eyes were enrolled. Ripasudil eye drops were administered to patients in both eyes. Phase 1 was a dose-escalation study (once daily for 1 week, then twice daily for 2 weeks); an additional dosing up to 9 weeks was allowed if no safety issues occurred. In phase 2, ripasudil was administered twice daily for up to 12 weeks. Adverse events were assessed. The proportion of patients with type 1 ROP progression, number of days for type 1 ROP progression, and progression to the most advanced ROP stage were estimated. RESULTS: Twenty-four infants were enrolled (phase 1, n = 3; phase 2, n = 21). Nineteen and four patients experienced systemic and ocular adverse events, respectively. Efficacy endpoints were not different between the ripasudil and historical control groups. However, in the GA ≤ 27 weeks subgroup, fewer patients progressed to type 1 ROP in the ripasudil than in the historical control group (P = 0.09). In the GA ≤ 27 weeks subgroups, the 25th percentile for the number of days for type 1 ROP progression was 22 days in the historical control group and 44 days in the ripasudil group. CONCLUSION: Ripasudil was safe and inhibited/delayed type 1 ROP progression, especially in infants with short GA.
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Natural killer (NK) cells lyse invading tumor cells to limit metastatic growth in the lung, but how some cancers evade this host protective mechanism to establish a growing lesion is unknown. Here, we have combined ultra-sensitive bioluminescence imaging with intravital two-photon microscopy involving genetically encoded biosensors to examine this question. NK cells eliminated disseminated tumor cells from the lung within 24 hr of arrival, but not thereafter. Intravital dynamic imaging revealed that 50% of NK-tumor cell encounters lead to tumor cell death in the first 4 hr after tumor cell arrival, but after 24 hr of arrival, nearly 100% of the interactions result in the survival of the tumor cell. During this 24-hr period, the probability of ERK activation in NK cells upon encountering the tumor cells was decreased from 68% to 8%, which correlated with the loss of the activating ligand CD155/PVR/Necl5 from the tumor cell surface. Thus, by quantitatively visualizing, the NK-tumor cell interaction at the early stage of metastasis, we have revealed the crucial parameters of NK cell immune surveillance in the lung.
Assuntos
Comunicação Celular/imunologia , Vigilância Imunológica , Microscopia Intravital/métodos , Células Matadoras Naturais/imunologia , Metástase Neoplásica/imunologia , Células Neoplásicas Circulantes/patologia , Animais , Técnicas Biossensoriais , Linhagem Celular Tumoral , Feminino , Proteínas Luminescentes , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND: Revesz syndrome is a rare type of the dyskeratosis congenita spectrum disorder that is characterized by nail dystrophy, oral leukoplakia, and abnormal skin pigmentation. The retinal features are similar to those of exudative retinopathy with avascular areas of the peripheral retina. There are only a few publications describing patients with Revesz syndrome who underwent ocular treatments for the retinal complications. We report a Case of Revesz syndrome with bilateral retinal detachments that were successfully reattached by pars plana vitrectomy. OBSERVATIONS: A 3-year-old Japanese girl with Revesz Syndrome had progressive vitreal hemorrhages and tractional retinal detachments in both eyes. She underwent pars plana vitrectomy with lensectomy on both eyes. A retinal attachment with vision improvement was achieved by a single surgery for the right eye and after repeated surgeries for the left eye. Postoperative electroretinographic (ERG) examinations of the right eye showed a negative type ERG with the b-wave/a-wave ratio <1.0. There were extensive areas of avascular retina detected by fluorescein angiography and a thinning of the inner and outer retina detected by optical coherence tomography. CONCLUSION AND IMPORTANCE: Pars plana vitrectomy can effectively treat the extensive retinal detachment in an eye with Revesz syndrome. However, postoperative retinal ischemia can be detected by careful imaging.
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BACKGROUND/OBJECTIVES: The prevalence of myopia is higher in preterm infants who underwent laser photocoagulation (LPC) for retinopathy of prematurity (ROP). The aim of this study was to investigate factors associated with myopia in preterm infants who undergo LPC for ROP. SUBJECTS/METHODS: We retrospectively analysed the medical records of preterm infants born at Kyushu University Hospital (October 2008-March 2018) at ≤32 weeks of gestational age or with birth weight ≤1500 g. We evaluated the associations between nine clinical factors and the spherical equivalent at 1-year corrected age by performing multivariable linear regression in LPC-treated ROP patients. RESULTS: Among the 485 infants enroled, 76 developed ROP requiring treatment. Of these, 71 underwent LPC, which was provided to 63 infants as the primary treatment (LPC alone or the combination therapy of LPC and intravitreal injection of bevacizumab [IVB]) and to eight infants as additional LPC after IVB monotherapy. The results of a refractive examination at 1-year corrected age were available for 110 eyes of 56 infants (78.9%). The mean ± standard deviation of the SE value was -0.5 ± 3.0 dioptres (D). Multivariable linear regression analysis revealed a significant association between laser spot count and SE value (ß = -0.081 ± 0.040 D per 100 spots [mean ± standard error], p = 0.045). CONCLUSIONS: Our results suggest that an increased laser spot count observed during ROP treatment associates with myopia.
Assuntos
Miopia , Retinopatia da Prematuridade , Inibidores da Angiogênese/uso terapêutico , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Injeções Intravítreas , Fotocoagulação a Laser , Lasers , Miopia/tratamento farmacológico , Miopia/cirurgia , Retinopatia da Prematuridade/tratamento farmacológico , Retinopatia da Prematuridade/epidemiologia , Retinopatia da Prematuridade/cirurgia , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: Pierson syndrome (PS) is a rare autosomal recessive disorder, characterized by congenital nephrotic syndrome and microcoria. Advances in renal replacement therapies have extended the lifespan of patients, whereas the full clinical spectrum of PS in infancy and beyond remains elusive. CASE PRESENTATION: We present the case of a 12-month-old boy with PS, manifesting as the bilateral microcoria and congenital nephrotic syndrome. He was born without asphyxia, and was neurologically intact from birth through the neonatal period. Generalized muscle weakness and hypotonia were recognized from 3 months of age. The infant showed recurrent vomiting at age 5 months of age, and was diagnosed with gastroesophageal reflux and intestinal malrotation. Despite the successful surgical treatment, vomiting persisted and led to severely impaired growth. Tulobuterol treatment was effective in reducing the frequency of vomiting. Targeted sequencing confirmed that he had a compound heterozygous mutation in LAMB2 (NM_002292.3: p.Arg550X and p.Glu1507X). A search of the relevant literature identified 19 patients with severe neuro-muscular phenotypes. Among these, only 8 survived the first 12 months of life, and one had feeding difficulty with similar gastrointestinal problems. CONCLUSIONS: This report demonstrated that severe neurological deficits and gastrointestinal dysfunction may emerge in PS patients after the first few months of life.
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Anormalidades Múltiplas/genética , Laminina/genética , Síndromes Miastênicas Congênitas/genética , Síndrome Nefrótica/genética , Distúrbios Pupilares/genética , Anormalidades Múltiplas/patologia , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/patologia , Humanos , Lactente , Masculino , Mutação , Síndromes Miastênicas Congênitas/patologia , Síndrome Nefrótica/patologia , Fenótipo , Distúrbios Pupilares/patologiaRESUMO
PURPOSE: The purpose of this study was to evaluate neurodevelopmental outcomes in 18-month old (corrected age) preterm infants who received an intravitreal bevacizumab (IVB) injection for the treatment of type 1 retinopathy of prematurity (ROP). METHODS: In this ten-year retrospective study, we reviewed the medical records of patients who underwent ROP screening at Kyushu University Hospital. Among the patients who received IVB or laser photocoagulation (LPC) for the treatment of type 1 ROP, we included infants whose neurodevelopmental examination (the Kyoto Scale of Psychological Development [KSPD]) results at 18 months corrected age were available. Then, the effect of IVB on the developmental quotient (DQ) in each KSPD domain (Postural-Movement, Cognitive-Adaptive, or Language-Social domain) or the overall DQ was investigated by performing linear regression analysis. RESULTS: Out of the 513 patients reviewed, 53 were included in the study. IVB and LPC were performed for 14 and 39 patients, respectively. Administration of IVB was significantly associated with neurodevelopmental delay in the Language-Social domain (p = 0.01). The observed association remained even after adjusting for gestational age and birth weight (p = 0.03). CONCLUSIONS: Administration of IVB may introduce a risk of developmental impairment of interpersonal relationships, socializations, and/or verbal abilities of preterm children. We recommended that preterm infants who received IVB undergo a neurodevelopmental reassessment during their school years or in adulthood.
Assuntos
Inibidores da Angiogênese/efeitos adversos , Bevacizumab/efeitos adversos , Deficiências do Desenvolvimento/etiologia , Retinopatia da Prematuridade/patologia , Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Injeções Intravítreas , Japão , Transtornos do Desenvolvimento da Linguagem/etiologia , Fotocoagulação a Laser , Análise Multivariada , Retinopatia da Prematuridade/tratamento farmacológico , Retinopatia da Prematuridade/cirurgia , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
Pierson syndrome, an autosomal recessive disorder caused by a mutation in laminin ß2 (LAMB2) gene, is characterized by congenital nephrotic syndrome and various ocular abnormalities. The ocular findings in Pierson syndrome are not well understood, because the incidence of this syndrome is very rare. We report ocular findings in a 5-month-old boy with Pierson syndrome with a novel mutation in LAMB2. We performed a pupilloplasty for his microcoria. Ophthalmic examinations after surgery revealed that he had cataract, severe retinal degeneration, and high myopia. Optical coherence tomography showed the collapse of retinal layer structures and a marked decrease of choroidal thickness. Immunohistochemistry and electron microscopy examinations revealed abnormal iris differentiation and thinning or defect of basal membranes. These results suggest that the development of the iris, lens, retina, and choroid are affected in this type of mutation.
Assuntos
Anormalidades Múltiplas , Catarata/patologia , Anormalidades do Olho , Laminina/genética , Mutação , Miopia Degenerativa/patologia , Síndrome Nefrótica , Distúrbios Pupilares , Degeneração Retiniana/patologia , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/patologia , Anormalidades do Olho/genética , Anormalidades do Olho/patologia , Humanos , Lactente , Masculino , Síndromes Miastênicas Congênitas , Síndrome Nefrótica/genética , Síndrome Nefrótica/patologia , Distúrbios Pupilares/genética , Distúrbios Pupilares/patologiaAssuntos
Lesões Encefálicas Traumáticas/etiologia , Lesões Encefálicas Traumáticas/patologia , Hemorragia Ocular/etiologia , Hemorragia Ocular/patologia , Traumatismos Cranianos Fechados/etiologia , Traumatismos Cranianos Fechados/patologia , Doenças da Esclera/etiologia , Doenças da Esclera/patologia , Idoso , Idoso de 80 Anos ou mais , Autopsia , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Hemorragia Ocular/diagnóstico por imagem , Evolução Fatal , Feminino , Traumatismos Cranianos Fechados/diagnóstico por imagem , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Doenças da Esclera/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
Visual loss caused by retinopathy of prematurity (ROP) will be prevented if treatment-requiring ROP (TR-ROP) can be predicted. In this retrospective study including 418 infants with ≤32 weeks of gestational age (GA) and/or ≤1500 grams of birthweight, we attempted to identify useful predictors. We also examined the efficiency of significant predictors compared with existing predictive models, ROPScore and CHOP model. Multivariable logistic regression analyses supported the following factors were useful for predicting TR-ROP from all infants and infants with any ROP: GA (odds ratio [OR], 0.47 and 0.48), history of late-onset circulatory collapse (LCC) (OR, 2.76 and 2.44) and use of continuous positive airway pressure (CPAP) at 35 weeks of postmenstrual age (OR, 3.78 and 4.50). The comparison of areas under receiver operating characteristic curves indicated the combination of LCC, CPAP and ROPScore was better than ROPScore to predict TR-ROP from all infants and infants with any ROP (P = 0.007 and 0.02) and the combination of LCC, CPAP and CHOP model was also better than CHOP model to predict TR-ROP from all infants and infants with any ROP (P = 0.01 and 0.02). Our results suggested infants with a history of LCC and a long CPAP support have a high incidence of TR-ROP.